Almotriptan Malate

Trade Names:Axert- Tablets 6.25 mg- Tablets 12.5 mg

Pharmacology

Selective agonist for vascular serotonin (5-HT) receptor subtype, causing vasoconstriction of cranial arteries.

Pharmacokinetics

Absorption

Well absorbed. Absolute bioavailability is about 70%. T _max is 1 to 3 h. C _max is 49.5 to 64 mcg/L.

Distribution

Approximately 35% is protein bound; Vd is approximately 180 to 200 L.

Metabolism

Metabolized to inactive metabolites by MAO-mediated oxidation (about 27%), CYP-450 (3A4 and 2D6)–mediated oxidation (about 12%), and flavin monooxygenase (minor).

Elimination

The mean half-life is 3 to 4 h. About 75% is excreted by the kidneys (about 40% as unchanged drug). About 13% is excreted in feces.

Special Populations

Cl is decreased approximately 65% in those with CrCl 10 to 30 mL/min and decreased approximately 40% in those with CrCl 31 to 71 mL/min. C _max increased approximately 80%.

The max decrease expected in almotriptan Cl due to hepatic function impairment would be 60%.

A longer terminal half-life (3.7 vs 3.2 h) and a 25% higher AUC has been observed in elderly patients.

No differences observed in rate or extent of absorption in adolescents compared with adults.

No gender differences have been observed.

No significant differences have been observed between black and white volunteers.

Indications and Usage

Acute treatment of migraine with or without aura in adults; acute treatment of migraine headache pain in adolescents with a history of migraine attacks, with or without aura, usually lasting 4 h or more (when untreated).

Contraindications

Ischemic heart disease (eg, angina pectoris, history of MI, documented silent ischemia); symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm (including Prinzmetal variant angina), or other significant underlying CV disease; cerebrovascular syndromes, including but not limited to stroke of any type as well as transient ischemic attacks; peripheral vascular disease, including but not limited to ischemic bowel disease; uncontrolled hypertension; use within 24 h of treatment with another 5-HT ₁ agonist or ergotamine-containing or ergot-type medication; hemiplegic or basilar migraine; hypersensitivity to any component of the product.

Dosage and Administration

PO 6.25 to 12.5 mg. If headache returns, may repeat dose after 2 h (max, 2 doses per 24 h).

PO 6.25 mg initially (max, 12.5 mg per 24 h).

General Advice

• Administer prescribed dose at onset of migraine symptoms.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

May cause prolonged vasospastic reactions; therefore, contraindicated within 24 h of almotriptan administration.

Almotriptan clearance may be decreased.

Use contraindicated within 24 h of each other.

Almotriptan plasma levels may be elevated, increasing the risk of adverse reactions.

Risk of life-threatening serotonin syndrome may be increased.

Almotriptan plasma concentrations may be increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension, palpitations, syncope, tachycardia, vasodilation; acute MI, angina pectoris, coronary artery vasospasm (postmarketing).

CNS

Somnolence (5%); dizziness (4%); headache (2%); paresthesia (1%).

EENT

Dry mouth (1%).

GI

Nausea (3%); vomiting (2%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 12 years of age.

Elderly

Use with caution, starting at the low end of the dosing range.

Hypersensitivity

Use with caution in patients with known hypersensitivity to sulfonamides. Cross-sensitivity has not been systematically evaluated.

Renal Function

Cl is reduced; use with caution.

Hepatic Function

Cl is reduced; use with caution.

Cardiac events/vasoconstriction

Serious coronary events, though rare, can occur after administration of 5-HT ₁ agonists. It is strongly recommended that almotriptan not be given to patients in whom unrecognized CAD is predicted by presence of risk factors (eg, hypertension, obesity). For patients with CAD risk factors, administer first dose in health care provider's office or similarly staffed and equipped facility. Consider obtaining an ECG during interval following administration of first dose of medication to patient with potential for CAD. Coronary artery vasospasm, acute MI, life-threatening cardiac rhythm disturbances, and death have been reported.

Vasospastic reactions such as peripheral and GI vascular ischemia with abdominal pain and bloody diarrhea may occur.

Cerebrovascular events

Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported with 5-HT ₁ agonists, and some events have resulted in fatalities.

Ophthalmic effects

Because almotriptan could accumulate in melanin-rich tissues over time, there is the possibility that it could causes toxicity in these tissues with extended use. Rare reports of transient and permanent blindness and significant partial vision loss have been reported with use of triptans.

Increased blood pressure

Significant elevations in systemic blood pressure have been reported on rare occasions in patients with and without a history of hypertension. Use is contraindicated in patients with uncontrolled hypertension.

Serotonin syndrome

Potentially life-threatening serotonin syndrome may occur, particularly during coadministration of SSRIs or SNRIs.

Overdosage

Symptoms

Hypertension, serious CV symptoms.

Patient Information

• Advise patient to read the patient information leaflet before starting therapy and again with each refill.
• Explain that drug is to be used only during migraine and does not prevent or reduce the number of attacks. Emphasize that drug is used only to treat actual migraine attack.
• Advise patient that drug is to be taken as soon as symptoms of migraine appear. Second dose may be taken if symptoms return, but no sooner than 2 h following first dose. For a given attack, if there is no response to first dose, do not take second dose without first consulting health care provider. Do not take more than 2 doses in any 24-h period.
• Advise patient that safety of treating more than 4 headaches in a 30-day period has not been established and to inform health care provider if headaches are occurring more frequently.
• Advise patient that if tightness, pain, pressure, or heaviness in chest or throat occurs when using almotriptan, notify health care provider before using drug again. Tell patient to notify health care provider immediately if chest pain is severe or does not go away.
• Advise patient to notify health care provider if feeling tingling, heat, heaviness, or pressure after treatment.
• Advise patient that drug may cause drowsiness or dizziness and to use caution while driving or performing other activities requiring mental alertness.
• Advise patient to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreen and wear protective clothing to avoid photosensitivity reactions.
• Instruct patient that if migraine prophylactic medications are prescribed, to continue to take daily as directed.
• Advise patient not currently taking a migraine prophylactic drug to discuss the use of such drugs with health care provider.

Copyright © 2009 Wolters Kluwer Health.